ArticleLeukemia2009
Repression of Gadd45alpha by activated FLT3 and GM-CSF receptor mutants contributes to growth, survival and blocked differentiation.
Article in Leukemia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Follicular Fluid-Derived Extracellular Vesicles Influence on In Vitro Maturation of Equine Oocyte: Impact on Cumulus Cell Viability, Expansion and Transcriptome.International journal of molecular sciences · 2024Article
- Gadd45 in Normal Hematopoiesis and Leukemia.Advances in experimental medicine and biology · 2022Article
- Gadd45 stress sensors in suppression of leukemia.Oncotarget · 2018Article
- GATA Regulation and Function During the Ovarian Life Cycle.Vitamins and hormones · 2018Review
- A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm.Scientific reports · 2017Article
- Genome-wide interactions between FSH and insulin-like growth factors in the regulation of human granulosa cell differentiation.Human reproduction (Oxford, England) · 2017Article
- Article
- FLT3 inhibitors: clinical potential in acute myeloid leukemia.OncoTargets and therapy · 2017Review
- Gaq signaling is required for the maintenance of MLL-AF9-induced acute myeloid leukemia.Leukemia · 2016Article
- MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α.Molecular cancer · 2015Article
- GADD45A methylation predicts poor overall survival in acute myeloid leukemia and is associated with IDH1/2 and DNMT3A mutations.Leukemia · 2013Article
- The Impact of FLT3 Mutations on the Development of Acute Myeloid Leukemias.Leukemia research and treatment · 2013Article
- C-terminal mutation of RUNX1 attenuates the DNA-damage repair response in hematopoietic stem cells.Leukemia · 2012Article
- The GM-CSF receptor utilizes β-catenin and Tcf4 to specify macrophage lineage differentiation.Differentiation; research in biological diversity · 2012Article
- Over-expression of Gadd45a enhances radiotherapy efficacy in human Tca8113 cell line.Acta pharmacologica Sinica · 2011Article
- Gadd45 stress sensors in malignancy and leukemia.Critical reviews in oncogenesis · 2011Review
- Stress sensor Gadd45 genes as therapeutic targets in cancer.Cancer therapy · 2009Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
The tumor suppressor Gadd45alpha was earlier shown to be a repressed target of sustained receptor-mediated ERK1/2 signaling. We have identified Gadd45alpha as a downregulated gene in response to constitutive signaling from two FLT3 mutants (FLT3-ITD and FLT3-TKD) commonly found in AML, and a leukemogenic GM-CSF receptor trans-membrane mutant (GMR-V449E). GADD45A mRNA downregulation is also associated with FLT3-ITD(+) AML. Sustained ERK1/2 signaling contributes significantly to receptor-mediated downregulation of Gadd45alpha mRNA in FDB1 cells expressing activated receptor mutants, and in the FLT3-ITD(+) cell line MV4;11. Knockdown of Gadd45alpha with shRNA led to increased growth and survival of FDB1 cells and enforced expression of Gadd45alpha in FDB1 cells expressing FLT3-ITD or GMR-V449E resulted in reduced growth and viability. Gadd45alpha overexpression in FLT3-ITD(+) AML cell lines also resulted in reduced growth associated with increased apoptosis and G(1)/S cell cycle arrest. Overexpression of Gadd45alpha in FDB1 cells expressing GMR-V449E was sufficient to induce changes associated with myeloid differentiation suggesting Gadd45alpha downregulation contributes to the maintenance of receptor-induced myeloid differentiation block. Thus, we show that ERK1/2-mediated downregulation of Gadd45alpha by sustained receptor signaling contributes to growth, survival and arrested differentiation in AML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.